Administration of pharmaceutical products containing a physiologically active peptide have been made, so far, by injection. In this context, lyophilization has exclusively been employed in the preparation of such pharmaceutical compositions. Thus, for such pharmaceutical compositions, studies addressed to the stabilization of their active components, physiologically active peptides, have so far been focused on either the long-term storage stability of the physiologically active peptides in a dry state pharmaceutical compositions of the final products, or the storage stability of the physiologically active peptides in liquids which are prepared by dissolving the peptide-containing dry compositions. For example, stabilization of calcitonin solutions is disclosed in Japanese Unexamined Patent Publication Nos. H07-179364, H07-188060 and H07-188061, and stabilization of lyophilized growth hormone products is disclosed in Japanese Unexamined Patent Publication Nos. H10-504531, H10-511965 and H10-507183.
The reason why injection has been the sole way for administering physiologically active peptides is that, when they are, orally administered, physiologically active peptides are digested in the gastrointestinal tract. A practically applicable new route for administration, if established, would provide a great benefit to patients. Above all, in the case of active peptides requiring lifelong administration such as growth hormone and insulin, the conventional way of administration of injection has been giving patients inconvenience and pain. For these physiologically active peptides, therefore, establishment of a route of administration other than injection has been longed for by the patients.
On the other hand, those pharmaceutical compositions for systemic administration of a drug are under investigation that are intended either for transpulmonary absorption of a pharmacologically active ingredient by inhalation (referred to as an “inhalant composition” in the present specification) or for absorption of such an ingredient through the nasal mucous membrane by intranasal application, i.e. compositions for transnasal administration, as compositions utilizing other, new administration routes than those relied on by conventional pharmaceutical compositions such as injections, oral preparations, suppositories and the like. Inhalant compositions and compositions for transnasal administration are not directly injected into the body, but they are applied onto the surface of mucous membranes which are exposed to the air such as membranes of the respiratory tract. Therefore, their standards for microbiological quality control are not so strict as those for injections. Thus, they may be produced not only by a lyophilization apparatus but also by a fluid-bed granulation apparatus, a spray drying apparatus, or a spray-freeze drying apparatus. Concerning stabilization of active peptides in production steps of pharmaceutical compositions using a fluid-bed granulation apparatus, a spray drying apparatus, or a spray-freeze drying apparatus, it is reported that stabilization is attained by addition of an inhibitor of Maillard reaction (Japanese Unexamined Patent Publication No. H10-505591). However, it is preferable, if possible, that stabilization of a given active peptide in a production process should be achieved by means of approved pharmaceutical additives which are highly safe and have been used for years. This is because such an additive would allow to expect higher safety with regard to the final pharmaceutical product obtained. It is also required that the absorption and transferal to the blood of an physiologically active peptide is attained in sufficient efficiency.
The present invention has as its objectives to provide a method to improve stability of a physiologically active peptide in a process of producing a powder by drying an aqueous liquid containing the physiologically active peptide, as well as to provide a physiologically active peptide-containing powder produced by the method.
The present invention has as its further objectives to provide a physiologically active peptide-containing powder especially suited for absorption of the physiologically active peptide by inhalation, and to provide an inhalant composition.